A comprehensive benchmark of graph-based genetic variant genotyping algorithms on plant genomes for creating an accurate ensemble pipeline.

BACKGROUND: Although sequencing technologies have boosted the measurement of the genomic diversity of plant crops, it remains challenging to accurately genotype millions of genetic variants, especially structural variations, with only short reads. In recent years, many graph-based variation genotyping methods have been developed to address this issue and tested for human genomes. However, their performance in plant genomes remains largely elusive. Furthermore, pipelines integrating the advantages of current genotyping methods might be required, considering the different complexity of plant genomes. RESULTS: Here we comprehensively evaluate eight such genotypers in different scenarios in terms of variant type and size, sequencing parameters, genomic context, and complexity, as well as graph size, using both simulated and real data sets from representative plant genomes. Our evaluation reveals that there are still great challenges to applying existing methods to plants, such as excessive repeats and variants or high resource consumption. Therefore, we propose a pipeline called Ensemble Variant Genotyper (EVG) that can achieve better genotyping performance in almost all experimental scenarios and comparably higher genotyping recall and precision even using 5× reads. Furthermore, we demonstrate that EVG is more robust with an increasing number of graphed genomes, especially for insertions and deletions. CONCLUSIONS: Our study will provide new insights into the development and application of graph-based genotyping algorithms. We conclude that EVG provides an accurate, unbiased, and cost-effective way for genotyping both small and large variations and will be potentially used in population-scale genotyping for large, repetitive, and heterozygous plant genomes.

Intestinal microbiota score could predict survival following allogeneic hematopoietic stem cell transplantation.

Intestinal microbiota is an important prognostic factor for allogeneic hematopoietic stem cell transplantation (allo-HSCT), but its role in predicting survival has not been determined. Here, stool samples at day 15 ± 1 posttransplant were obtained from 209 patients at two centers. Microbiota was examined using 16S rRNA sequencing. The microbiota diversity and abundance of specific bacteria (including Lachnospiraceae, Ruminococcaceae, Erysipelotrichaceae, and Enterobacteriaceae) were assigned a value of 0 or 1 depending on whether they were positive or negative associated with survival, respectively. An accumulated intestinal microbiota (AIM) score was generated, and patients were divided into low- and high-score groups. A low score was associated with a better 3-year cumulative overall survival (OS) as well as lower mortality than a high score (88.5 vs. 43.9% and 7.1 vs. 35.8%, respectively; both P < 0.001). In multivariate analysis, a high score was found to be an independent risk factor for OS and transplant-related mortality (hazard ratio = 5.68 and 3.92, respectively; P < 0.001 and 0.003, respectively). Furthermore, the AIM score could serve as a predictor for survival (area under receiver operating characteristic curve = 0.836, P < 0.001). Therefore, the intestinal microbiota score at neutrophil recovery could predict survival following allo-HSCT.

Ponatinib therapy in recurrent Philadelphia chromosome-positive central nervous system leukemia with T315I mutation after Allo-HSCT.

Central nervous system leukemia (CNSL) relapse is relatively common among Philadelphia chromosome-positive (Ph+) leukemia patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). The prognosis of patients is dismal for those with a BCR-ABL T315I mutation, which is resistant to TKIs including second-generation drugs. We assessed ponatinib for nine patients with recurrent Ph+ CNSL and a T315I mutation after allo-HSCT, including five patients with Ph+ acute lymphoblastic leukemia and four with chronic myelogenous leukemia. Five patients experienced isolated CNSL relapse, and four experienced CNSL with hematologic relapse. All patients received ponatinib combined with intrathecal chemotherapy, and four patients with hematologic relapse received systemic chemotherapy and/or donor lymphocyte infusion. All patients achieved a deep molecular response and central nervous system remission (CNSR) at a median time of 1.5 (range: 0.7-3) months after ponatinib treatment. Two patients experienced a second CNSL relapse due to ponatinib reduction, but they achieved CNSR again after an increase to the standard dosage. Six patients developed graft versus host disease. By April 1, 2019, eight patients were alive, and one died of pneumonia. The median time of survival after the first CNSL relapse posttransplantation was 18 (range: 11.2-48.5) months. Our data from a small number of samples suggests that ponatinib is effective for recurrent Ph+ CNSL patients with a BCR-ABL T315I mutation after allo-HSCT and warrants broader clinical evaluation.

[Size distributions and diurnal variations in the concentrations of polycyclic aromatic hydrocarbons in winter in urban and suburban Nanjing, China].

The contamination status and distribution characteristics of particulate polycyclic aromatic hydrocarbons (PAHs) were investigated in aerosols of urban and suburban Nanjing. A total of 17 PAHs were analyzed in the aerosol samples collected in daytime and nighttime during January 1st to 10th, 2010 in Nanjing University (NU) and Nanjing University of Information Science & Technology (NUIST). The PAH concentrations at the urban and suburban sites were 41.36-220.35 ng x m(-3) and 45.10-200.86 ng x m(-3), respectively, of which about 66%-67% was absorbed by fine particles (Dp < or = 2.1 microm). High levels of particulate PAHs were detected at both sampling sites with different diurnal variations. The higher total-PAH concentration occurred in the daytime at the urban site and in the nighttime at the suburban site. The change of prevailing wind direction and high-pressure weather system had significant impact on the variation of PAH concentrations, which were dominated by fine and coarse particles in urban and suburban regions, respectively. Difference in PAH size distributions was found for low weight molecular PAHs (LWM-PAH) and high weight molecular PAHs (HWM-PAH) in urban and suburban areas. The concentrations of 2-3 ring PAHs were higher at the suburban site than those at the urban site, whereas larger amounts of 4-6 ring PAHs were found at the urban site than at the suburban site. The concentration peaks in coarse particle size of high-molecular-weight PAHs found in our study were larger than those in some of the previous studies, which might be due to the high carbon content in coarse particles in the atmosphere at our sites. Analysis of diagnostic ratios indicated that the PAHs particles at both two sites have the same sources, including combustion of coal and biomass, vehicular exhaust and suburban industrial emission.